High Dosage of Experimental Drug Blamed for Temporary Outcome
A clinical trial involving gene therapy for a condition linked to autism has been paused after two test subjects temporarily lost their ability to walk. The trial by the biopharmaceutical company Ultragenyx and biotech startup GeneTx focused on Angelman Syndrome, a rare genetic neurodevelopmental condition characterized by intellectual disability, balance issues, motor problems, seizures, and insomnia. These symptoms are also common in autism. While environmental factors seem to play a large role in autism causation, Angelman Syndrome has a purely genetic etiology. A mutation on the UBE3A gene has been identified in the syndrome which results in no active UBE3A proteins being present in brain cells. Ultragenyx and GeneTx developed an experimental drug called GTX-102 to try to restore the UBE3A protein to typical levels. The clinical GTX-102 trial involved five individuals with Angelman Syndrome, ages 5 to 15. These subjects received one injected dose of the drug in the lower back once a month, over four months. When the clinical trial experimented with differing dosage levels, all five participants experienced leg weakness with two losing the ability to walk while on the higher dosages of the drug. This side effect appears to be the result of inflamed nerves at the injection site. All five participants recovered once drugs to decrease inflammation were administered. This setback, while serious, is not the end of the road for GTX-102. All five subjects showed significant improvements in communication, sleep and motor skills while on the drug. From here on out, Ultragenyx and GeneTx plan to limit the maximum dose to the range that did not cause leg weakness but improved skills in its participants.
